Are We Making Mountains Out of Molehills?
When most of us think about manufacturing
or aseptic processing, we envision large-scale
bulk formulation or fills that take longer
than 24 hours. But is this what a product
looks like for everyone? After all, not every
company focuses on large-scale bulk products,
some specialize in small-scale products.
Does this mean the regulations change if we
go from large-scale to small-scale? In other
words, are we scaling mountains to meet requirements
that do not pertain to molehills?
The goal of an aseptic operation is to
prevent the contamination of materials
intended to be sterile. This is where process
verification testing becomes important.
For large-scale automated operations with
infrequent operator interventions, determining
if the process can produce sterile
products requires analyzing large-scale
automated media fills that resemble normal
production. Small-scale processes using all
or partial manual procedures must also be
evaluated by process verification testing.
Manual operations present unique operational
and evaluation challenges not
generally encountered with automated
operations. Manual aseptic processes rely
heavily on the proficiency of the individual
operator. Operations personnel
and their activities are generally recognized
as the greatest source of microbial
contamination during any given process.
Reproducible human performance cannot
be assumed over time. In other words, unlike
automated processes, humans cannot
be “validated.” We can be qualified and
tested, but we humans cannot provide the
reproducibility of an automated system.
In effect, what does this mean and how
can we state that our drug products are
safe, pure and effective if we cannot
validate the manual or human aspect of
our process? To achieve these key regulatory
criteria, special attention to operator
training and qualifications, as well
as length of time away from/or absence
from the process must be considered.
Operator training should be extensive and
include multiple challenges of all critical
steps to a point of proficiency. Training
must include qualifications not limited to
gowning procedures, technique and media
challenges. Documentation must include
a list of all critical steps trained on, how
many times an operator showed proficiency
prior to final evaluation and length
of time away from the process.
This process takes into account a number
- Is this product manufactured or processed
daily, monthly or as needed by
- What if an operator is away from the
manual process for any length of time?
- What steps are needed to ensure the operators
retained all critical steps during
their time away from the process?
- How is this process documented?
The PDA Education course, “Recommended
Practices for Manual Aseptic
Processes,” addresses these and other
challenges facing operators during smallscale
runs. It not only covers the requirements
of how to perform a manual aseptic
process but also provides students with
a hands-on laboratory media challenge.
This course is designed for operations
personnel who design, perform and evaluate
manual aseptic processes—including
personnel involved with compounding,
filling, packaging and quality assurance
operations, and is suitable for supervisors
and managers as well as personnel engaged
in manual processing operations.